KIF5CKinesin family member 5C
Autism Reports / Total Reports
7 / 14Rare Variants / Common Variants
34 / 0Aliases
KIF5C, FLJ44735, KIAA0531, KINN, MGC111478, NKHC, NKHC-2, NKHC2Associated Syndromes
-Chromosome Band
2q23.1-q23.2Associated Disorders
ASD, EP, EPSRelevance to Autism
A de novo missense variant in the KIF5C gene that was predicted to be damaging was identified in an autistic proband (Awadalla et al., 2010). Inherited missense variants in this gene that were predicted to be damaging were identified in Chinese ASD probands in Li et al., 2017. Phenotypic characterization of four previously published cases (from de Ligt et al., 2013, Poirier et al., 2013, Januar et al., 2014, and Cavallin et al., 2016) and two novel cases in Michels et al., 2017 implicated KIF5C missense variants as the cause of a neurodevelopmental disorder characterized by infantile-onset epilepsy, absent speech, malformations of cortical development, and, in three cases, stereotypic hand movements.
Molecular Function
Neuron-specific kinesin heavy chain (kinesin is a microtubule-associated force-producing protein that may play a role in organelle transport)
External Links
SFARI Genomic Platforms
Reports related to KIF5C (14 Reports)
# | Type | Title | Author, Year | Autism Report | Associated Disorders |
---|---|---|---|---|---|
1 | Primary | Direct measure of the de novo mutation rate in autism and schizophrenia cohorts | Awadalla P , et al. (2010) | Yes | - |
2 | Support | Diagnostic exome sequencing in persons with severe intellectual disability | de Ligt J , et al. (2012) | No | Epilepsy, ASD |
3 | Support | Mutations in TUBG1, DYNC1H1, KIF5C and KIF2A cause malformations of cortical development and microcephaly | Poirier K , et al. (2013) | No | Epilepsy/seizures |
4 | Support | Somatic mutations in cerebral cortical malformations | Jamuar SS , et al. (2014) | No | Pachygyria |
5 | Support | Recurrent KIF5C mutation leading to frontal pachygyria without microcephaly | Cavallin M , et al. (2015) | No | Absent speech, stereotypic hand movements, pachygy |
6 | Support | Targeted sequencing and functional analysis reveal brain-size-related genes and their networks in autism spectrum disorders | Li J , et al. (2017) | Yes | - |
7 | Recent Recommendation | Mutations of KIF5C cause a neurodevelopmental disorder of infantile-onset epilepsy, absent language, and distinctive malformations of cortical development | Michels S , et al. (2017) | No | Absent speech, stereotypic hand movements |
8 | Support | Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes | Feliciano P et al. (2019) | Yes | - |
9 | Support | Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders | Wang T et al. (2020) | Yes | - |
10 | Support | - | Brunet T et al. (2021) | No | - |
11 | Support | - | Li W et al. (2021) | No | - |
12 | Support | - | Zhou X et al. (2022) | Yes | - |
13 | Support | - | Chen WX et al. (2022) | Yes | - |
14 | Support | - | Sanchis-Juan A et al. (2023) | Yes | - |
Rare Variants (34)
Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
---|---|---|---|---|---|---|---|---|
c.510T>C | p.Thr170%3D | stop_lost | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.768T>C | p.Asn256%3D | stop_lost | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.1361A>T | p.Glu454Val | stop_lost | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.1431T>C | p.Asn477%3D | stop_lost | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.217+1G>A | - | splice_site_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.1200C>T | p.Asp400%3D | stop_gained | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.2331G>T | p.Arg777Ser | stop_gained | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.2463C>T | p.Asn821%3D | stop_gained | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.200C>T | p.Ala67Val | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.571C>T | p.Arg191Ter | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.802G>A | p.Ala268Thr | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.857G>A | p.Arg286Gln | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.1351G>C | p.Asp451His | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.1810C>T | p.Arg604Cys | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.2830G>T | p.Gly944Trp | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
C>T | R802C, R872C | missense_variant | De novo | - | - | 20797689 | Awadalla P , et al. (2010) | |
c.420G>A | p.Arg141Gln | missense_variant | De novo | - | - | 23033978 | de Ligt J , et al. (2012) | |
c.513G>T | p.Cys172Phe | missense_variant | Unknown | - | - | 25140959 | Jamuar SS , et al. (2014) | |
c.420G>A | p.Arg141Gln | missense_variant | De novo | - | - | 29048727 | Michels S , et al. (2017) | |
c.1918G>A | p.Ser640= | missense_variant | De novo | - | - | 31452935 | Feliciano P et al. (2019) | |
c.1824C>T | p.Leu608%3D | stop_gained | Familial | Paternal | - | 33004838 | Wang T et al. (2020) | |
c.2439G>T | p.Gly814Val | missense_variant | Unknown | - | - | 23033978 | de Ligt J , et al. (2012) | |
c.420G>A | p.Arg141Gln | missense_variant | De novo | - | - | 26384676 | Cavallin M , et al. (2015) | |
c.1783C>T | p.Asp595= | missense_variant | Familial | - | Simplex | 28831199 | Li J , et al. (2017) | |
c.1344A>G | p.Glu449Gly | missense_variant | Familial | - | Simplex | 28831199 | Li J , et al. (2017) | |
c.2385C>T | p.Ala796Val | missense_variant | Familial | - | Simplex | 28831199 | Li J , et al. (2017) | |
c.2541G>A | p.Arg848Lys | missense_variant | Familial | - | Simplex | 28831199 | Li J , et al. (2017) | |
c.160C>T | p.Pro54Ser | missense_variant | De novo | - | Multiplex | 35982159 | Zhou X et al. (2022) | |
c.323T>A | p.Ile108Asn | missense_variant | De novo | - | Multiplex | 35982159 | Zhou X et al. (2022) | |
c.1996G>A | p.Glu666Lys | missense_variant | De novo | - | Simplex | 36320054 | Chen WX et al. (2022) | |
c.420G>A | p.Leu140%3D | missense_variant | De novo | - | Unknown | 33619735 | Brunet T et al. (2021) | |
- | - | complex_structural_alteration | Unknown | - | Simplex | 37541188 | Sanchis-Juan A et al. (2023) | |
c.542T>G | p.Met181Arg | missense_variant | Unknown | - | Simplex | 37541188 | Sanchis-Juan A et al. (2023) | |
c.710A>T | p.Glu237Val | missense_variant | De novo (germline mosaicism) | - | Multiplex | 23603762 | Poirier K , et al. (2013) |
Common Variants
No common variants reported.
SFARI Gene score
Strong Candidate, Syndromic
A de novo missense variant in the KIF5C gene that was predicted to be damaging was identified in an autistic proband (Awadalla et al., 2010). Inherited missense variants in this gene that were predicted to be damaging were identified in Chinese ASD probands in Li et al., 2017. Phenotypic characterization of four previously published cases (from de Ligt et al., 2013, Poirier et al., 2013, Januar et al., 2014, and Cavallin et al., 2016) and two novel cases in Michels et al., 2017 implicated KIF5C missense variants as the cause of a neurodevelopmental disorder characterized by infantile-onset epilepsy, absent speech, malformations of cortical development, and, in three cases, stereotypic hand movements.
Score Delta: Score remained at 2S
criteria met
See SFARI Gene'scoring criteriaWe considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.
The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."
4/1/2022
Decreased from 3S to 2S
Description
A de novo missense variant in the KIF5C gene that was predicted to be damaging was identified in an autistic proband (Awadalla et al., 2010). Inherited missense variants in this gene that were predicted to be damaging were identified in Chinese ASD probands in Li et al., 2017. Phenotypic characterization of four previously published cases (from de Ligt et al., 2013, Poirier et al., 2013, Januar et al., 2014, and Cavallin et al., 2016) and two novel cases in Michels et al., 2017 implicated KIF5C missense variants as the cause of a neurodevelopmental disorder characterized by infantile-onset epilepsy, absent speech, malformations of cortical development, and, in three cases, stereotypic hand movements.
1/1/2021
Decreased from 3S to 3S
Description
A de novo missense variant in the KIF5C gene that was predicted to be damaging was identified in an autistic proband (Awadalla et al., 2010). Inherited missense variants in this gene that were predicted to be damaging were identified in Chinese ASD probands in Li et al., 2017. Phenotypic characterization of four previously published cases (from de Ligt et al., 2013, Poirier et al., 2013, Januar et al., 2014, and Cavallin et al., 2016) and two novel cases in Michels et al., 2017 implicated KIF5C missense variants as the cause of a neurodevelopmental disorder characterized by infantile-onset epilepsy, absent speech, malformations of cortical development, and, in three cases, stereotypic hand movements.
10/1/2020
Decreased from 3S to 3S
Description
A de novo missense variant in the KIF5C gene that was predicted to be damaging was identified in an autistic proband (Awadalla et al., 2010). Inherited missense variants in this gene that were predicted to be damaging were identified in Chinese ASD probands in Li et al., 2017. Phenotypic characterization of four previously published cases (from de Ligt et al., 2013, Poirier et al., 2013, Januar et al., 2014, and Cavallin et al., 2016) and two novel cases in Michels et al., 2017 implicated KIF5C missense variants as the cause of a neurodevelopmental disorder characterized by infantile-onset epilepsy, absent speech, malformations of cortical development, and, in three cases, stereotypic hand movements.
10/1/2019
Decreased from 4S to 3S
New Scoring Scheme
Description
A de novo missense variant in the KIF5C gene that was predicted to be damaging was identified in an autistic proband (Awadalla et al., 2010). Inherited missense variants in this gene that were predicted to be damaging were identified in Chinese ASD probands in Li et al., 2017. Phenotypic characterization of four previously published cases (from de Ligt et al., 2013, Poirier et al., 2013, Januar et al., 2014, and Cavallin et al., 2016) and two novel cases in Michels et al., 2017 implicated KIF5C missense variants as the cause of a neurodevelopmental disorder characterized by infantile-onset epilepsy, absent speech, malformations of cortical development, and, in three cases, stereotypic hand movements.
7/1/2018
Increased from to 4S
Description
A de novo missense variant in the KIF5C gene that was predicted to be damaging was identified in an autistic proband (Awadalla et al., 2010). Inherited missense variants in this gene that were predicted to be damaging were identified in Chinese ASD probands in Li et al., 2017. Phenotypic characterization of four previously published cases (from de Ligt et al., 2013, Poirier et al., 2013, Januar et al., 2014, and Cavallin et al., 2016) and two novel cases in Michels et al., 2017 implicated KIF5C missense variants as the cause of a neurodevelopmental disorder characterized by infantile-onset epilepsy, absent speech, malformations of cortical development, and, in three cases, stereotypic hand movements.
Krishnan Probability Score
Score 0.61320097232496
Ranking 146/25841 scored genes
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ExAC Score
Score 0.99951559715187
Ranking 932/18225 scored genes
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Sanders TADA Score
Score 0.94145518732924
Ranking 14939/18665 scored genes
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Larsen Cumulative Evidence Score
Score 2
Ranking 393/461 scored genes
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Zhang D Score
Score 0.42920690030661
Ranking 1130/20870 scored genes
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